Thyroid hormones triiodothyronine (T3) and its prohormone thyroxine (T4) are derivatives of the amino acid tyrosine. T4 is produced by the thyroid gland, and metabolized by peripheral tissues to T3. Thyroid hormones are of widespread biological effect on the growth and development and metabolic processes of many different organs and tissues. Deficiencies in T3 and/or T4 are associated with hypothyroidism, the symptoms of which include tiredness, cold sensitivity, weight gain, goiter, decreased muscle tone, myxedema, decreased motor skills, and cretinism.
Levothyroxine sodium is a synthetic form of thyroxine commonly administered to patients suffering from hypothyroidism in thyroid hormone replacement therapy. Levothyroxine is also known as 3,5,3′,5′-tetraiodo-L-thyronine, synthetic T4, and L-thyroxine; and the sodium salt of levothyroxine has the chemical formula:

The objective of thyroid hormone replacement therapy is restoration of a euthyroid state. It is, however, well known that levothyroxine has a narrow therapeutic index. The package inserts for several FDA-approved, oral levothyroxine products instruct that, regardless of the indication for use, careful dosage titration is necessary to avoid the consequences of over-treatment or under-treatment. These consequences include, among others, effects on growth and development, cardiovascular function, bone metabolism, reproductive function, cognitive function, emotional state, gastrointestinal function, and glucose and lipid metabolism.
Oral levothyroxine solutions have certain advantages over solid dosage forms. For instance, levothyroxine solutions possess greater potency uniformity than tablets. Tablets often have very low levothyroxine content, which leads to difficulties in achieving drug content uniformity in the manufacturing process. Such that the actual levothyroxine dose that a patient receives with tablet therapy can deviate from label amounts by 20%. Whereas it is much more facile to manufacture homogeneous levothyroxine solutions. In addition, many patients have greater difficulty swallowing tablets than solutions, especially children and the elderly.
Oral levothyroxine solutions also have certain disadvantages compared to solid dosage forms, such as decreased storage stability. But even levothyroxine tablets are known to have storage stability problems. And several regulatory agency approved brands have been subjected to recall due to failure to maintain potency through the expiration date.
The extent of levothyroxine's potency uniformity and storage stability problems is reflected in the United States Food and Drug Administration's (FDA) 1997 action of categorizing all orally administered levothyroxine sodium drug products as new drugs due to significant storage stability and variable potency problems. The FDA required manufacturers of levothyroxine drug products who wished to continue marketing them to submit new drug applications. (See, 62 Fed. Reg. 43535 (Aug. 14, 1997).) In 2012, the United Kingdom's Medicines and Healthcare Products Regulatory Agency issued a Class 2 recall against EVOTROX 25, 50, and 100 microgram levothyroxine solutions because variable stability data failed to provide assurance of product quality.